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NAPSB 作为预测标志物,与肝癌中免疫热肿瘤微环境相关的预后和治疗。

NAPSB as a predictive marker for prognosis and therapy associated with an immuno-hot tumor microenvironment in hepatocellular carcinoma.

机构信息

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuhan, 430071, Hubei Province, China.

Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China.

出版信息

BMC Gastroenterol. 2022 Aug 20;22(1):392. doi: 10.1186/s12876-022-02475-8.

Abstract

BACKGROUND

Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined.

METHODS

The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort. Kaplan-Meier analyses, and univariate and multivariate Cox regression were conducted to determine the prognosis value of NAPSB on patients with HCC. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed by bioinformatics methods.

RESULTS

NAPSB was downregulated in patients with HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells, T cell inflamed score and cancer-immunity cycle, and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis.

CONCLUSIONS

NAPSB was correlated with an immuno-hot and inflamed TME, and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.

摘要

背景

天冬氨酸蛋白酶 Napsin B 假基因(NAPSB)与胰腺导管腺癌中的 CD4+T 细胞浸润有关。然而,NAPSB 在肝细胞癌(HCC)中的生物学作用仍有待确定。

方法

使用来自多个公共数据集的数据分析 HCC 中 NAPSB 的表达及其与临床病理的关联。使用 Zhongnan 队列通过 qRT-PCR 验证 HCC 患者中 NAPSB 的相对表达。进行 Kaplan-Meier 分析、单因素和多因素 Cox 回归分析以确定 NAPSB 对 HCC 患者的预后价值。然后进行富集分析以确定 NAPSB 的可能生物学功能。随后,全面展示 NAPSB 在 HCC 肿瘤微环境(TME)中的免疫特征。通过生物信息学方法分析 NAPSB 在预测热肿瘤中的作用及其对免疫治疗和化疗反应的影响。

结果

NAPSB 在 HCC 患者中下调,高 NAPSB 表达显示出改善的生存结果。富集分析表明 NAPSB 与免疫激活有关。NAPSB 与免疫调节剂、肿瘤浸润免疫细胞、T 细胞炎症评分和癌症免疫循环呈正相关,并且在免疫热肿瘤中高表达。NAPSB 高表达对免疫治疗和化疗敏感,可能与其与细胞焦亡、细胞凋亡和细胞坏死有关。

结论

NAPSB 与免疫热和炎症 TME 以及肿瘤细胞死亡有关。它可以作为 HCC 预后和治疗的有前途的预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d162/9392949/54c89a41fb87/12876_2022_2475_Fig1_HTML.jpg

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